Epigenetics Flashcards
What is epigenetics?
Mechanisms enabling heritable transfer of gene expression profiles by adaptation of chromatin without influencing underlying DNA sequence.
What is chromatin?
The complex of DNA and proteins that forms chromosomes within the nucleus of eukaryotic cells.
What are the characteristics of euchromatin?
More dispersed, less heavily stained under EM, gene rich, transcriptionally active, more unique DNA sequences, often found in the center of the nucleus.
What are the characteristics of heterochromatin?
Condensed appearance, very densely stained under EM, gene poor, transcriptionally inactive, repetitive DNA sequences.
What are the two types of heterochromatin?
Constitutive: always condensed, near telomeres. Facultative: become repressed, can be activated.
What is a nucleosome?
The fundamental unit of chromatin.
What is the structure of a nucleosome?
Protein octamer containing H2A, H2B, H3, H4 x2; 2 wraps of DNA of 146 bp; H1 protein binds to linker DNA – another 20 bp.
What is the role of histone tails?
Basic amino acids at N terminal stick out from the core, serving as a primary level of regulation and allowing higher order organization.
What are histone modifications?
Chemical modifications to histone proteins that can affect gene expression.
What is histone acetylation?
The addition of acetyl groups to histones, which introduces a negative charge and loosens up the chromatin complex.
Who are the writers of histone acetylation?
Histone acetyl-transferases (HATs) use a cofactor Acetyl-CoA to introduce acetyl groups.
What is the role of histone deacetylases (HDACs)?
They remove acetyl groups, closing up chromatin and inactivating gene expression.
What are bromodomain proteins?
Readers that bind to acetylated histones and help recruit transcriptional machinery to promoters and enhancers.
What is the effect of histone methylation on gene expression?
It is context dependent, varying based on which residue is methylated and the degree of methylation.
What is the MLL chromatin complex?
A histone methyltransferase that can bind to H3K4 mono/di-methyl and then methylate it again.
What are Trithorax and Polycomb genes?
Genes important in development for expression of HOX genes, with Trithorax activating and Polycomb repressing gene expression.
What are nucleosome remodellers?
Proteins that affect higher order interactions without chemically adding groups onto histone proteins.
What is the function of SWI/SNF family nucleosome remodellers?
They contain bromodomain to bind acetylated histones and are associated with opening chromatin.
What is the role of transcription co-activators?
They can have histone modifying activity, such as CBP, which is a coactivator and histone acetyltransferase.
What is DNA methylation?
Modification of cytosine to 5-methylcytosine by DNA methyltransferase.
What are CpG islands?
Regions of DNA with a high concentration of CpG sites, often unmethylated in constitutively expressed genes.
What is the function of DNA methylation?
Prevents some transcription factors from binding to DNA, leading to long-term gene inactivation.
What is genomic imprinting?
The expression of only one of the maternal or paternal alleles.
What is the role of DNMT1?
Maintenance of methylation patterns after DNA replication.
What is the effect of dysregulation of DNA methylation in cancer?
Methylation of tumor suppressor genes and hypo-methylation of oncogene regulatory regions can lead to cancer.
What are epigenetic drugs?
Drugs that target epigenetic modifications, such as iDNMTs and iHDACs, to reactivate silenced tumor suppressor genes.
